METTL3/IGF2BP2 Promotes the Malignant Progression of Esophageal Cancer by Activating the PIK3CA/AKT Pathway.

IF 2.3 3区医学 Q3 ONCOLOGY Thoracic Cancer Pub Date : 2025-02-01 DOI:10.1111/1759-7714.70022

Xinmeng Guo, Anqi Huang, Ya'nan Qi, Jiaqi Chen, Meng Yang, Mulan Jin

{"title":"METTL3/IGF2BP2 Promotes the Malignant Progression of Esophageal Cancer by Activating the PIK3CA/AKT Pathway.","authors":"Xinmeng Guo, Anqi Huang, Ya'nan Qi, Jiaqi Chen, Meng Yang, Mulan Jin","doi":"10.1111/1759-7714.70022","DOIUrl":null,"url":null,"abstract":"<p><p>Esophageal cancer (EC) is a leading cause of cancer-related mortality worldwide. Methyltransferase-like 3 (METTL3), a key enzyme involved in m6A methylation, has been implicated in the development and progression of various cancers, including EC. However, its potential mechanism of action in EC progression remains unclear. METTL3 expression was found to be upregulated in EC tissues and cells. Knockdown of METTL3 suppressed EC cell proliferation, invasion, migration, and angiogenesis, while promoting apoptosis. Mechanistically, METTL3 maintained PIK3CA mRNA expression and stability in an m6A-dependent and IGF2BP2-dependent manner, respectively. METTL3 silencing inactivated the AKT pathway by regulating PIK3CA expression. Furthermore, overexpression of PIK3CA mitigated the effects of METTL3 silencing on the malignant growth of KYSE180 and TE1 cells in vivo and in vitro. METTL3/IGF2BP2 promoted the malignant progression of EC by activating the PIK3CA/AKT pathway. Targeting the METTL3-PIK3CA axis may offer a novel therapeutic approach for EC treatment.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 4","pages":"e70022"},"PeriodicalIF":2.3000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842509/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Thoracic Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/1759-7714.70022","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Esophageal cancer (EC) is a leading cause of cancer-related mortality worldwide. Methyltransferase-like 3 (METTL3), a key enzyme involved in m6A methylation, has been implicated in the development and progression of various cancers, including EC. However, its potential mechanism of action in EC progression remains unclear. METTL3 expression was found to be upregulated in EC tissues and cells. Knockdown of METTL3 suppressed EC cell proliferation, invasion, migration, and angiogenesis, while promoting apoptosis. Mechanistically, METTL3 maintained PIK3CA mRNA expression and stability in an m6A-dependent and IGF2BP2-dependent manner, respectively. METTL3 silencing inactivated the AKT pathway by regulating PIK3CA expression. Furthermore, overexpression of PIK3CA mitigated the effects of METTL3 silencing on the malignant growth of KYSE180 and TE1 cells in vivo and in vitro. METTL3/IGF2BP2 promoted the malignant progression of EC by activating the PIK3CA/AKT pathway. Targeting the METTL3-PIK3CA axis may offer a novel therapeutic approach for EC treatment.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

METTL3/IGF2BP2通过激活PIK3CA/AKT通路促进食管癌恶性进展

食管癌（EC）是全球癌症相关死亡的主要原因。甲基转移酶样3 （METTL3）是参与m6A甲基化的关键酶，与包括EC在内的各种癌症的发生和进展有关。然而，其在EC进展中的潜在作用机制尚不清楚。METTL3在EC组织和细胞中表达上调。敲低METTL3抑制EC细胞的增殖、侵袭、迁移和血管生成，同时促进细胞凋亡。在机制上，METTL3分别以m6a依赖和igf2bp2依赖的方式维持PIK3CA mRNA的表达和稳定性。METTL3沉默通过调节PIK3CA表达使AKT通路失活。此外，在体内和体外实验中，PIK3CA过表达减轻了METTL3沉默对KYSE180和TE1细胞恶性生长的影响。METTL3/IGF2BP2通过激活PIK3CA/AKT通路促进EC的恶性进展。靶向METTL3-PIK3CA轴可能为EC治疗提供一种新的治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

文献相关原料

公司名称

产品信息

索莱宝

propidium iodide

来源期刊

Thoracic Cancer ONCOLOGY-RESPIRATORY SYSTEM

CiteScore

5.20

自引率

3.40%

发文量

439

审稿时长

2 months

期刊介绍： Thoracic Cancer aims to facilitate international collaboration and exchange of comprehensive and cutting-edge information on basic, translational, and applied clinical research in lung cancer, esophageal cancer, mediastinal cancer, breast cancer and other thoracic malignancies. Prevention, treatment and research relevant to Asia-Pacific is a focus area, but submissions from all regions are welcomed. The editors encourage contributions relevant to prevention, general thoracic surgery, medical oncology, radiology, radiation medicine, pathology, basic cancer research, as well as epidemiological and translational studies in thoracic cancer. Thoracic Cancer is the official publication of the Chinese Society of Lung Cancer, International Chinese Society of Thoracic Surgery and is endorsed by the Korean Association for the Study of Lung Cancer and the Hong Kong Cancer Therapy Society. The Journal publishes a range of article types including: Editorials, Invited Reviews, Mini Reviews, Original Articles, Clinical Guidelines, Technological Notes, Imaging in thoracic cancer, Meeting Reports, Case Reports, Letters to the Editor, Commentaries, and Brief Reports.